rs13079478

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024513.4(FYCO1):c.3003C>A(p.Asn1001Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,613,960 control chromosomes in the GnomAD database, including 13,741 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1001D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.088 ( 971 hom., cov: 33)

Exomes 𝑓: 0.12 ( 12770 hom. )

Consequence

FYCO1
NM_024513.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.322

Variant links:

Genes affected

FYCO1 (HGNC:14673): (FYVE and coiled-coil domain autophagy adaptor 1) The gene encodes a Rab7 adapter protein that is implicated in the microtubule transport of autophagosomes. The encoded protein contains a RUN domain, a FYVE-type zinc finger domain, and Golgi dynamics (GOLD) domain. The encoded protein plays a role in microtubule plus end-directed transport of autophagic vesicles through interactions with the small GTPase Rab7, phosphatidylinositol-3-phosphate (PI3P), the autophagosome marker LC3, and the kinesin KIF5. Mutations in this gene are associated with inclusion body myositis (IBM) and autosomal recessive congenital cataracts (CATC2). [provided by RefSeq, Aug 2020]

FYCO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032511652).

BP6

Variant 3-45966331-G-T is Benign according to our data. Variant chr3-45966331-G-T is described in ClinVar as [Benign]. Clinvar id is 261729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-45966331-G-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYCO1	NM_024513.4 link	c.3003C>A	p.Asn1001Lys	missense_variant	Exon 8 of 18	ENST00000296137.7	NP_078789.2	Q9BQS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYCO1	ENST00000296137.7 link	c.3003C>A	p.Asn1001Lys	missense_variant	Exon 8 of 18	1	NM_024513.4	ENSP00000296137.2		Q9BQS8-1

Frequencies

GnomAD3 genomes

AF:

0.0885

AC:

13468

AN:

152166

Hom.:

972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.0644

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.0908

GnomAD3 exomes

AF:

0.124

AC:

31070

AN:

249724

Hom.:

3025

AF XY:

0.139

AC XY:

18806

AN XY:

135120

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.0609

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.00266

Gnomad SAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.115

AC:

168149

AN:

1461676

Hom.:

12770

Cov.:

AF XY:

0.123

AC XY:

89680

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.0628

Gnomad4 ASJ exome

AF:

0.180

Gnomad4 EAS exome

AF:

0.00204

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.0884

AC:

13461

AN:

152284

Hom.:

971

Cov.:

AF XY:

0.0944

AC XY:

7029

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0178

Gnomad4 AMR

AF:

0.0642

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.00366

Gnomad4 SAS

AF:

0.342

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.0918

Alfa

AF:

0.105

Hom.:

1394

Bravo

AF:

0.0716

TwinsUK

AF:

0.0992

AC:

368

ALSPAC

AF:

0.0986

AC:

380

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.126

AC:

15337

Asia WGS

AF:

0.169

AC:

588

AN:

3478

EpiCase

AF:

0.119

EpiControl

AF:

0.113

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 18

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0055

.;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.93

N;N

REVEL

Benign

0.11

Sift

Benign

0.098

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.0080

.;B

Vest4

0.025

MutPred

0.25

Gain of ubiquitination at N1001 (P = 0.0022);Gain of ubiquitination at N1001 (P = 0.0022);

MPC

0.19

ClinPred

0.00044

GERP RS

1.4

Varity_R

0.066

gMVP

0.067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over